A Randomized Study of the Safety, Tolerability, and Pharmacokinetics of AZ-009 (Staccato Apomorphine) in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZ-009 in Subjects With Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- B-Dose Proportionality by Power Analysis of AUCinf
研究概览
简要总结
This study will be conducted in 3 parts. A) compare the pharmacokinetics (PK) of a single dose of AZ-009 with that of a therapeutically-relevant dose of a commercially available apomorphine injector in healthy volunteers; B) ascending doses of active drug in healthy volunteers; and C) examine the tolerability, safety, and PK of AZ-009 in subjects with established Parkinson's disease.
详细描述
This study will be conducted in 3 parts. Parts A and B will be conducted in healthy volunteers and Part C will be conducted in subjects with established Parkinson's disease. The primary objectives for each part are as follows.
Part A: To compare the pharmacokinetics of a single low dose of AZ-009 with that of a therapeutically-relevant dose a commercially available apomorphine injector in healthy volunteers.
Part B: To examine the tolerability and safety of AZ-009 of single ascending doses of active drug in healthy volunteers while; and to characterize the pharmacokinetics of single ascending doses of AZ-009 in healthy volunteers
Part C: To examine the tolerability, safety, and pharmacokinetics of AZ-009 in subjects with established Parkinson's disease and to identify optimal doses to bring into multiple ascending dose safety and efficacy studies; and to assess the usability of AZ-009 in subjects with Parkinson's Disease
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult males and females between 18 and 60 years of age, inclusive at the time of signing the informed consent document.
- •Body weight ≥ 50 kg and BMI within the range of 18 to 32 kg/m
- •Willing and able to be confined at the clinical research center for the study period and adhere to overall study visit schedule, procedures and other protocol requirements.
- •Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
排除标准
- •Any significant medical condition, psychiatric illness or history of depression that could, in the investigator's opinion, compromise the subject's safety or interfere with the completion of this protocol.
- •History of clinically significant central nervous system, cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions including gastric bypass or other weight loss surgical procedure; or history of such conditions that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial.
- •Use of non-prescription medications within 5 days prior to the first dose of study drug.
- •Use of medication that is inhibitor or inducer of CYP450-3A4/5 within 3 days of dosing.
- •Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, within 3 days prior to administration of study drug.
研究组 & 干预措施
C-1p (009-0)
Part C, Arm 1 (Inhaled placebo)
干预措施: 009-0 (Drug)
C-2a (009-4)
Part C, Arm 2 (Inhaled apomorphine, Dose 4)
干预措施: 009-4 (Drug)
A-1 (009-1 -> active comparator)
Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)
干预措施: 009-1 (Drug)
A-1 (009-1 -> active comparator)
Part A, Arm 1 (Inhaled apomorphine, Dose 1 followed by commercially available active comparator)
干预措施: active comparator (Drug)
A-2 (active comparator -> 009-1)
Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)
干预措施: 009-1 (Drug)
A-2 (active comparator -> 009-1)
Part A, Arm 2 (commercially available active comparator followed by Inhaled apomorphine, Dose 1)
干预措施: active comparator (Drug)
B-1a (009-2)
Part B, Arm 1 (Inhaled apomorphine, Dose 2)
干预措施: 009-2 (Drug)
B-1p (009-0)
Part B, Arm 1 (Inhaled placebo)
干预措施: 009-0 (Drug)
B-2a (009-3)
Part B, Arm 2 (Inhaled apomorphine, Dose 3)
干预措施: 009-3 (Drug)
B-2p (009-0)
Part B, Arm 2 (Inhaled placebo)
干预措施: 009-0 (Drug)
B-3a (009-4)
Part B, Arm 3 (Inhaled apomorphine, Dose 4)
干预措施: 009-4 (Drug)
B-3p (009-0)
Part B, Arm 3 (Inhaled placebo)
干预措施: 009-0 (Drug)
C-1a (009-3)
Part C, Arm 1 (Inhaled apomorphine, Dose 3)
干预措施: 009-3 (Drug)
C-2p (009-0)
Part C, Arm 2 (Inhaled placebo)
干预措施: 009-0 (Drug)
C-3a (009-5)
Part C, Arm 3 (Inhaled apomorphine, Dose 5)
干预措施: 009-5 (Drug)
C-3p (009-0)
Part C, Arm 3 (Inhaled placebo)
干预措施: 009-0 (Drug)
结局指标
主要结局
B-Dose Proportionality by Power Analysis of AUCinf
时间窗: 24 hours
Dose proportionality of inhaled Staccato apomorphine AUCinf across all doses administered in the single ascending dose portions of the study (Parts B and C) using a power model \[regression of log(AUCinf) versus log(dose)\]
A-Relative bioavailability of inhaled Staccato apomorphine dose compared to the subcutaneous administration
时间窗: 24 hours
Relative bioavailability of inhaled Staccato apomorphine compared to active comparator injection based on the Geometric Least Squares Mean Ratio of AUCinf for all subjects completing the crossover part of the trial
次要结局
未报告次要终点